The present invention relates to novel arylpyrazoles, compositions containing them, processes for their preparation, and their uses as insecticides and nematicides.
This invention relates to 1-arylpyrazole derivatives, to compositions containing them and to the use of said compounds and compositions against arthropods, particularly insects and nematodes.
U.S. Pat. No. 5,232,940 describes N-phenylpyrazoles with, among others, 5-cycloalkylcarbonyl and 5-alkoxycarbonyl substituents.
DE 3509567 and EP 382034 describe 3-nitro-1-phenylpyrazoles as herbicides and insecticides.
DE 2701091 describes fungicidal pyrazoles with amides at positions 4 or 5.
EP 202169 describes 1-(4-alkoxy)phenyl pyrazoles as herbicides.
EP 398499 describes cyano-phenylpyrazoles as insecticides.
None of the foregoing publications describes or suggests that compounds of formula (I) possess or would be expected to possess activity against arthropods, especially insects or nematodes.
This invention provides novel arylpyrazoles of the formula (I): 
wherein
R1 is selected from cyano, halogen, formyl, C(O)R2, H, and R2;
R2 is selected from C1-C4 alkyl, C1-C4 haloalkyl, and cycloalkyl optionally substituted with one or more halogens;
R3 is selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, nitro, CONR4R5, COOR4, and xe2x80x94S(O)nR6;
R4 and R5 are independently selected from H, C1-C5 alkyl, and C1-C5 haloalkyl;
R6 is selected from C1-C4 alkyl, C1-C4 haloalkyl, and cycloalkyl optionally substituted with one or more halogens;
R7 is selected from C(O)R8, C1-C6 xcex1-hydroxyalkyl, C1-C6 xcex1-hydroxyhaloalkyl, C(OR9)xe2x95x90CHR10, CHR11R12, xe2x80x94CR13xe2x95x90ND and 
R8 is selected from H, C1-C5 alkyl, and C1-C5 haloalkyl;
R9 is selected from C(O)R18, CHO, xe2x80x94S(O)2R18, xe2x80x94S(O)2aryl, C3-C18 trialkylsilyl, C8-C18 dialkylarylsilyl, C13-C20 diarylalkylsilyl and C18-C24 triarylsilyl;
R10 is selected from H, C1-C4 alkyl, and C1-C4 haloalkyl;
R11 and R12 are independently selected from C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, NR8R10, C3-C8 trialkylsiloxy and cyano;
R13 is selected from H, C1-C5 alkyl, and C1-C5 haloalkyl;
R14 is selected from H, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, cyano and nitro;
R15 and R17 are independently selected from H and halogen;
R16 is selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, cyano, nitro, C(O)R18, and xe2x80x94S(O)qR19;
R18 is selected from C1-C3 alkyl and C1-C3 haloalkyl;
R19 is selected from C1-C3 alkyl and C1-C3 haloalkyl;
X is selected from a nitrogen atom or Cxe2x80x94R20;
R20 is selected from H, halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;
A and E are independently selected from NR21, O and S;
R21 is selected from H, C1-C4 alkyl and C1-C4 haloalkyl;
D is selected from OR22 and NR23R24;
R22, R23 and R24 are independently selected from H, C1-C4 alkyl, and C1-C4 haloalkyl;
Z is (CH2)m;
m is 2, 3 or 4;
n is 0, 1 or 2;
q is 0, 1 or 2;
and pesticidally acceptable salts thereof;
provided that:
R11 and R12 are always the same except when R12 is cyano; and
R4 is not H when R3 is COOR4.
By the term xe2x80x9cpesticidally acceptable saltsxe2x80x9d is meant salts the anions of which are known and accepted in the art for the formation of pesticidally acceptable salts. Preferably such salts are water soluble. Suitable acid addition salts, formed by compounds of formula (I) containing an amine group, include salts with inorganic acids, for example hydrochlorides, phosphates, sulfates, nitrates; and salts with organic acids, for example acetates.
In this specification, xe2x80x9chalogenxe2x80x9d means the atoms fluorine, chlorine, bromine and iodine. Alkyl groups and moieties may be either linear or branched chain. xe2x80x9cCycloalkylxe2x80x9d means a cycloalkyl group having from three to seven carbon atoms in the ring, each of which optionally bears one or more C1-C4 alkyl. xe2x80x9cArylxe2x80x9d means phenyl optionally substituted by one or more of the members of the group consisting of C1-C4 alkyl and halogen which may be the same or different. It will be understood that in certain cases, compounds of formula (I) can be present in the form of optical and/or stereoisomers. All such forms are embraced by the invention.
Compounds of formula (I) above in which R7 is formyl generally possess a lower level of activity as insecticides but are useful as intermediates in the preparation of more highly active species.
It will be understood that the provisos appearing in the above description are present for reasons of biological efficacy and synthetic accessiblity.
A feature of the invention are those compounds having one or more of the following features:
R1 is cyano;
R3 is xe2x80x94S(O)nR6;
R7 is selected from the group C(O)R8, C1-C6 xcex1-hydroxyalkyl, C1-C6 xcex1-hydroxyhaloalkyl, C(OR9)xe2x95x90CHR10, CHR11R12, and xe2x80x94CR13xe2x95x90ND;
R14 is halogen;
R15 and R17 are H;
R16 is C1-C4 haloalkyl; and
X is Cxe2x80x94R20.
Preferred compounds of formula (I) above are compounds wherein:
R1 is selected from cyano, halogen, C(O)R2, H, and R2;
R3 is xe2x80x94S(O)nR6;
R7 is selected from C(O)R8, xe2x80x94CR13xe2x95x90ND, and xe2x80x94CHR11R12;
R14 is halogen;
R15 and R17 are H; and
R16 is C1-C4 haloalkyl.
A further preferred class of compounds of formula (I) are those wherein:
R1 is cyano;
R3 is xe2x80x94S(O)nR6;
R6 is C1-C2 haloalkyl, preferably CF3;
R7 is selected from C(O)R8, xe2x80x94CHR11R12 and xe2x80x94CR13xe2x95x90ND;
R11 is C1-C4 alkoxy;
R12 is selected from C1-C4 alkoxy and cyano;
R14 is halogen;
R15 and R17 are H;
R16 is C1-C2 haloalkyl, especially CF3.
THe numbers 1-21 are assigned to these compounds for reference and identification. Hereinafter compounds of fomrula (I) include the following:
1. 5-Acetyl-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfonylpyrazole, m.p. about 161xc2x0 C.;
2. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-formyl-4-trifluoromethylthiopyrazole, m.p. about 90xc2x0 C.;
3. 5-{(N-amino)iminomethylidenyl}-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole, m.p. about 130xc2x0 C.;
4. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethoxymethyl-4-trifluoromethylthiopyrazole, m.p. about 93xc2x0 C.;
5. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-{(N-methoxy)iminomethylidenyl}-4-trifluoromethylthiopyrazole, m.p. about 87xc2x0 C.;
6. 3-Cyano-5-{(1-cyano-1-methoxy)methyl}-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole, an oil;
7. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(hydroxy)methyl-4-trifluoromethylthiopyrazole, m.p. about 118xc2x0 C.;
8. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(1-hydroxy)ethyl-4-trifluoromethylthiopyrazole, m.p. about 123xc2x0 C.;
9. 5-Acetyl-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole, m.p. about 128xc2x0 C.;
10. 5-Acetyl-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinylpyrazole, m.p. 156xc2x0 C.;
11. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N,N-dimethylaminoiminomethylidenyl)-4-trifluoromethylthiopyrazole, m.p. about 126xc2x0 C.
12. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(hydroxy)methyl-4-trifluoromethylsulfinylpyrazole, m.p. about 153xc2x0 C.;
13. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethoxymethyl-4-trifluoromethylsulfinylpyrazole, m.p. about 116xc2x0 C.;
14. 3-Cyano-5-{(1-cyano-1-methoxy)methyl}-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinylpyrazole, m.p. about 167xc2x0 C.;
15. 3-Cyano-1-(2,6-dichloro-4-trifluoromethlphenyl)-5-dimethoxymethyl-4-trifluoromethylsulfonylpyrazole, m.p. 137xc2x0 C.;
16. 3-Cyano-5-{(1-cyano-1-methoxy)methyl}-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfonylpyrazole, m.p. 90xc2x0 C.;
17. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(1-hydroxy-2,2,2-trifluoroethyl)-4-trifluoromethylthiopyrazole, m.p. about 106xc2x0 C.;
18. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-diethoxymethyl-4-trifluoromethylthiopyrazole, m.p. about 72xc2x0 C.;
19. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-diethoxymethyl-4-trifluoromethylsulfonylpyrazole, m.p. about 100xc2x0 C.;
20. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-diethoxymethyl-4-trifluoromethylsulfinylpyrazole, m.p. 132xc2x0 C.;
21. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(1-acetoxyethenyl)-4-trifluoromethylsulfonylpyrazole, m.p. 121xc2x0 C.;
It is an object of the present invention to provide new pesticidal compounds of the 1-arylpyrazole family together with processes for their preparation.
A second object of the present invention is to provide pesticidal compositions and pesticidal methods of use of the pesticidal pyrzole compounds against arthropods, especically insects, plant nematodes, or helminth or protozoan pests, particularly in agricultural or horticultural crops, forestry, veterinary medicine or livestock husbandry, or in public health.
A third object of the present invention is to provide very active compounds, with broad spectrum pesticidal activity, as well as compounds with selective special activity, e.g., aphicidal, foliar insecticidal, soil insecticidal and nematicidal, systemic, antifeeding or pesticidal activity via seed treatment.
A fourth object of the present invention is to provide compounds with substantially enhanced and more rapid activity, especially against insects and more particularly insects in their larval stages.
A fifth object of the present invention is to provide compounds with greatly improved (greater and faster) penetration into pest species when topically applied and thus to provide enhanced movement of the compounds to the pesticidal site(s) of action within the pest.
Another object of the present invention is to provide compounds with high activity and improved safety to the user and the environment, which are obtained by optimization of chemical, physical and biological properties such as solubility, melting point, stability, electronic and steric parameters, and the like.
These objects are achived, in whole or in part, by the present invention.
The compounds of formula (I) can be prepared by the application or adaptation of known methods (i.e., methods heretofore used or described in the chemical literature): generally pyrazole ring formation followed where necessary by changing substituents. It is also to be understood that, in the description of the following processes the sequences for the introduction of the various groups on the pyrazole ring may be performed in a different order and that suitable protecting groups may be required as will be apparent to those skilled in the art.
In the following description of processes when symbols appearing in formulae are not specifically defined, it is to be understood that they are xe2x80x9cas defined abovexe2x80x9d in accordance with the first definition of each symbol in this specification. The term xe2x80x9cprotectionxe2x80x9d shall include conversion to a stuitable non-reactive group which may be reconverted when desired, as well as the addition of groups which render the functionality non-reactive.
In the description that follows, the ring system: 
is defined as Q.
According to a feature of the present invention compounds of formula (I) wherein R7 is formyl are formed by oxidative cleavage of the alkene moiety of a compound of formula (II): 
wherein R25 is selected from alkylcarbonyl, alkoxycarbonyl, cyano and nitro. When R25 is alkylcarbonyl or alkoxycarbonyl, it is preferably (C1-C12 alkyl)carbonyl or (C1-C12 alkoxy)carbonyl, most preferably (C1-C6 alkyl)carbonyl or (C1-C6 alkoxy)carbonyl. Such a transformation is well known to those skilled in the art and can be realized with ozone, potassium permanganate, sodium metaperiodate and the like. The process may be carried out optionally in a solvent such as methylene chloride, diethyl ether or chloroform and generally at temperatures between xe2x88x92100xc2x0 C. and 100xc2x0 C. A summary of such methods is found in Comprehensive Organic Transformations, VCH Publishers, 1989, R. C. Larock, pp. 595-596.
Compounds of formula (II) are novel and constitute a further feature of the invention. Compounds of formula (II) can be prepared by dehydrohalogenation of a compound of formula (III): 
wherein xe2x80x9chaloxe2x80x9d represents halogen and R25 is defined as above.
This can be effected by reaction of formula (III) compounds with bases such as triethylamine, sodium hydroxide and lithium diisopropylamide. The reaction is carried out optionally in a common organic solvent such as dichloromethane, diethyl ether, tetrahydrofuran, or toluene, and generally between xe2x88x92100 and 100xc2x0 C. depending on the base used. Compounds of formula (III) are novel and constitute a further feature of the invention.
Compounds of formula (III) can be produced from compounds of formula (IV): 
The process is effected by reaction of a compound of formula (IV) with an olefin of formula (V) in the presence of an alkylnitrite and Copper (II) halide, for example, as described in J. Org. Chem., 1977, 42 (14) 2431. Those skilled in the art will recognize this as a Meerwein Arylation. The process is generally carried out in a mixture of the olefin and a common organic solvent, preferably acetonitrile. The process is generally carried out at a temperature from xe2x88x9250 to 100xc2x0 C., preferably at ambient temperature.
Syntheses of compounds of formula (V) are described in U.S. Pat. Nos. 5,232,940; 5,306,694; 4,772,312; 4,804,675; and 4,614,533.
According to a further feature of the present invention, compounds of formula (I) above in which R7 is xe2x80x94CHR11R12 wherein R11 and R12 are not cyano and are the same, or in which R7 is 
may be prepared by the reaction of the corresponding compound of formula (I) above in which R7 is formyl with a compound of formula (VIa) or (VIb) respectively, wherein R11 is not cyano: 
in the presence of a catalyst, such as sulfuric acid, hydrochloric acid, para-toluenesulfonic acid, an acidic resin or a Lewis acid catalyst such as zinc (II) chloride. The process is generally carried out optionally in the presence of a solvent such as dichloromethane or benzene and occurs from xe2x88x9220xc2x0 C. to 100xc2x0 C., preferably at the boiling point of the solvent. Those skilled in the art will recognize this reaction as an acetal formation, the general conditions of which are found in Protective Groups in Organic Synthesis, 2nd Ed., Wiley-Interscience, 1991, T. W. Greene and P. G. M. Wuts; pp. 175-220. Compounds of formulae (VIa) and (VIb) are known to those skilled in the art as alcohols, amines and thiols.
According to a further feature of the present invention, compounds of formula (I) above in which R7 is xe2x80x94CHR11(CN) may be prepared from the corresponding compound of formula (I) in which R7 is xe2x80x94CHR11R12 in which R11 and R12 are the same, by treatment with a trialkylsilylcyanide in the presence of an acid catalyst, preferably a Lewis acid catalyst, e.g. a group IIB, IIA, or IVA halide, such as titanium tetrachloride, in a solvent such as dichloromethane or acetonitrile. Such a process is carried out from xe2x88x9230 to 100xc2x0 C., preferably from 0xc2x0 to xe2x88x9220xc2x0 C. and is described in Tetrahedron Lett., 1984, 25 (31) 3301; Chem. Lett., 1984, 897, and Bull. Chem. Soc. Jpn., 1990, 63, 3122.
According to a further feature of the present invention, compounds of formula (I) above in which R7 is C1-C6 xcex1-hydroxyalkyl or C1-C6 xcex1-hydroxyhaloalkyl may be prepared by the reaction of the corresponding compound of formula (I) in which R7 is formyl with an organometallic reagent or hydride of formula R8-M, wherein M is an alkali or transition metal. The reaction may be performed in a solvent such as a dialkyl ether (e.g. diethyl ether), tetrahydrofuran (THF), or a hydrocarbon (e.g. hexane or toluene) or mixtures thereof. A temperature of from xe2x88x92100xc2x0 C. to the reflux temperature of the solvent system is generally used.
According to a further feature of the present invention, compounds of formula (I) above in which R7 is C(O)R8 may be prepared by the oxidation of a compound of formula (I) wherein R7 is C1-C6 xcex1-hydroxyalkyl or C1-C6 xcex1-hydroxyhaloalkyl.
This is a reaction well known to those skilled in the art, a summary of which is given in Comprehensive Organic Transformation, VCH Publishers, 1989, R. C. Larock, pp. 604-614.
According to a further feature of the present invention, compounds of formula (I) in which R7 is CR13xe2x95x90ND may be prepared by the reaction of the corresponding compound of formula (I) in which R7 is C(O)R8 respectively with a compound of formula (VII):
Dxe2x80x94NH2xe2x80x83xe2x80x83(VII) 
The process is generally carried out optionally in the presence of a solvent such as ethanol, methylene chloride, or toluene and generally at temperatures between 0xc2x0 C. and the reflux temperature of the solvent. Those skilled in the art will recognize such reactions as formations of oximes and hydrazones whose methods of synthesis are reviewed in Advanced Organic Chemistry, 4th ed., J. Wiley and Sons, 1992, March, pp. 804-806. Compounds of formula (VII) are well known to those skilled in the art or may be prepared by known methods.
According to a further feature of the present invention, compounds of formula (I) above in which R7 is xe2x80x94C(OR9)xe2x95x90CHR10 may be prepared by the reaction of the corresponding compound of formula (I) in which R7 is C(O)R8 (and R8 is not H) with a base, followed by treatment with a compound of formula R9xe2x80x94L, wherein L is a leaving group, such as halide anion or sulfonate anion. Suitable bases include triethylamine and lithium diisopropylamide. The process is generally carried out within a range of temperatures, usually between xe2x88x92100xc2x0 C. and the boiling temperature of the solvent, such as tetrahydrofuran, toluene, diethyl ether and the like. Modern Organic Chemistry, 2nd ed., Benjamin Cummings, 1972, H. O. House, p. 763 describes a similar process.
Pesticidally acceptable salts of the compounds of formula (I) may be prepared by known methods.
The following compounds are further examples of the invention. In the table that follows the following abbreviations have been used:
Me=methyl
Et=ethyl
Pr=n-propyl